XIAP regulates bi-phasic NF-kappaB induction involving physical interaction and ubiquitination of MEKK2.
Cell Signal
; 20(11): 2107-12, 2008 Nov.
Article
em En
| MEDLINE
| ID: mdl-18761086
ABSTRACT
The transcription factor NF-kappaB is transiently activated by a wide variety of stress signals, including pro-inflammatory mediators, and regulates the expression of genes with e.g., immune, inflammatory, and anti-apoptotic functions. The strength and kinetics of its induction, as well as its ultimate down-regulation is subject to multiple levels of regulation. One such regulatory protein is X chromosome-linked inhibitor of apoptosis (XIAP) that, besides its anti-apoptotic properties, has been shown to enhance NF-kappaB activity, however, the underlying molecular mechanism has remained elusive. We show here that following TNFalpha stimulation XIAP regulates a second wave of NF-kappaB activation. XIAP interacts with and ubiquitinates MEKK2, a kinase that has previously been associated with bi-phasic NF-kappaB activation. We conclude that, through interaction with MEKK2, XIAP functions in an ubiquitin ligase dependent manner to evoke a second wave of NF-kappaB activation, resulting in the modulation of NF-kappaB target gene expression.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
NF-kappa B
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MAP Quinase Quinase Quinases
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Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X
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Ubiquitinação
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cell Signal
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Áustria